Study to Evaluate the Safety and Efficacy of E/C/F/TAF (Genvoya®) Versus E/C/F/TDF (Stribild®) in HIV-1 Positive, Antiretroviral Treatment-Naive Adults
- Conditions
- HIVHIV Infections
- Interventions
- Drug: E/C/F/TAFDrug: E/C/F/TDFDrug: E/C/F/TAF PlaceboDrug: E/C/F/TDF Placebo
- Registration Number
- NCT01780506
- Lead Sponsor
- Gilead Sciences
- Brief Summary
The primary objective of this study is to evaluate the efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) versus elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) FDC in HIV-1 positive, antiretroviral treatment-naive adults.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 872
- Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
- Plasma HIV-1 RNA levels ≥ 1,000 copies/mL at screening
- No prior use of any approved or investigational antiretroviral drug for any length of time, except the use for pre-exposure prophylaxis (PREP) or post-exposure prophylaxis (PEP), up to 6 months prior to screening
- Screening genotype report must show sensitivity to elvitegravir, emtricitabine, tenofovir disoproxil fumarate (tenofovir DF)
- Normal electrocardiogram (ECG)
- Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance
- Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN)
- Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
- Adequate hematologic function
- Serum amylase ≤ 5 × ULN
- Males and females of childbearing potential must agree to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 30 days following the last dose of study drug
- Females who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing
- Females who have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal failure must have a serum follicle stimulating hormone (FSH) level at screening within the post-menopausal range based on the Central Laboratory reference range
Key
- A new acquired immunodeficiency syndrome (AIDS) defining condition diagnosed within the 30 days prior to screening
- Hepatitis B surface antigen (HBsAg) positive
- Hepatitis C antibody positive
- Individuals experiencing decompensated cirrhosis
- Females who are breastfeeding
- Positive serum pregnancy test
- Have an implanted defibrillator or pacemaker
- Current alcohol or substance use judged by the Investigator to potentially interfere with study compliance
- History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma
- Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
- Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the individual unsuitable for the study or unable to comply with dosing requirements
- Participation in any other clinical trial (including observational trials) without prior approval
- Individuals receiving ongoing therapy with drugs not to be used with elvitegravir, cobicistat, emtricitabine, tenofovir DF, and TAF or individuals with any known allergies to the excipients of E/C/F/TDF or E/C/F/TAF single-tablet regimen tablets
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description E/C/F/TDF (Double-Blind Phase) E/C/F/TAF Placebo E/C/F/TDF plus E/C/F/TAF placebo for 144 weeks E/C/F/TAF (Double-Blind Phase) E/C/F/TAF E/C/F/TAF plus E/C/F/TDF placebo for 144 weeks E/C/F/TAF (Double-Blind Phase) E/C/F/TDF Placebo E/C/F/TAF plus E/C/F/TDF placebo for 144 weeks E/C/F/TDF (Double-Blind Phase) E/C/F/TDF E/C/F/TDF plus E/C/F/TAF placebo for 144 weeks Open-Label Extension Phase E/C/F/TAF After study unblinding, participants who complete 144 weeks of the study had the option to receive open-label E/C/F/TAF until commercially available, or until Gilead Sciences terminated the study in that country.
- Primary Outcome Measures
Name Time Method Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 Week 48 The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline in Hip BMD at Week 144 Baseline; Week 144 Hip BMD was assessed by DXA scan.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 96 and 144 Weeks 96 and 144 The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Weeks 96 and 144 were analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Weeks 48, 96, and 144 Weeks 48, 96. and 144 The percentage of participants achieving HIV-1 RNA \< 20 copies/mL at Weeks 48, 96, and 144 were analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Change From Baseline in CD4+ Cell Count at Week 48 Baseline; Week 48 Percent Change From Baseline in Spine BMD at Week 48 Baseline; Week 48 Spine BMD was assessed by DXA scan.
Percent Change From Baseline in Urine RBP to Creatinine Ratio at Week 144 Baseline; Week 144 Urine RBP is a renal biomarker which is used to detect drug-induced kidney injury.
Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio at Week 48 Baseline; Week 48 Urine Beta-2-microglobulin is a renal biomarker which is used to detect drug-induced kidney injury.
Percent Change From Baseline in Spine BMD at Week 96 Baseline; Week 96 Spine BMD was assessed by DXA scan.
Change From Baseline in Serum Creatinine at Week 48 Baseline; Week 48 Change From Baseline in CD4+ Cell Count at Week 96 Baseline; Week 96 Change From Baseline in CD4+ Cell Count at Week 144 Baseline; Week 144 Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 Baseline; Week 48 Hip BMD was assessed by dual energy x-ray absorptiometry (DXA) scan.
Percent Change From Baseline in Hip BMD at Week 96 Baseline; Week 96 Hip BMD was assessed by DXA scan.
Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio at Week 96 Baseline; Week 96 Urine Beta-2-microglobulin is a renal biomarker which is used to detect drug-induced kidney injury.
Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio at Week 144 Baseline; Week 144 Urine Beta-2-microglobulin is a renal biomarker which is used to detect drug-induced kidney injury.
Percent Change From Baseline in Spine BMD at Week 144 Baseline; Week 144 Spine BMD was assessed by DXA scan.
Change From Baseline in Serum Creatinine at Week 96 Baseline; Week 96 Change From Baseline in Serum Creatinine at Week 144 Baseline; Week 144 Percentage of Participants Experiencing Treatment-emergent Proteinuria Through Week 48 Up to 48 weeks Grades 1 (mild), 2 (moderate), and 3 (severe) were the highest treatment-emergent postbaseline grades for urine protein using the dipstick method. The worst postbaseline value is presented for each participant.
Percentage of Participants Experiencing Treatment-emergent Proteinuria Through Week 96 Up to 96 weeks Grades 1 (mild), 2 (moderate), and 3 (severe) were the highest treatment-emergent postbaseline grades for urine protein using the dipstick method. The worst postbaseline value is presented for each participant.
Percentage of Participants Experiencing Treatment-emergent Proteinuria Through Week 144 Up to 144 weeks Grades 1 (mild), 2 (moderate), and 3 (severe) were the highest treatment-emergent postbaseline grades for urine protein using the dipstick method. The worst postbaseline value is presented for each participant.
Percent Change From Baseline in Urine Retinol Binding Protein (RBP) to Creatinine Ratio at Week 48 Baseline; Week 48 Urine RBP is a renal biomarker which is used to detect drug-induced kidney injury.
Percent Change From Baseline in Urine RBP to Creatinine Ratio at Week 96 Baseline; Week 96 Urine RBP is a renal biomarker which is used to detect drug-induced kidney injury.
Trial Locations
- Locations (117)
Kaiser Permanente Los Angeles
🇺🇸Los Angeles, California, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Mercer University School of Medicine
🇺🇸Macon, Georgia, United States
Anthony Mills MD Inc
🇺🇸Los Angeles, California, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Ruth M. Rothstein CORE Center
🇺🇸Chicago, Illinois, United States
Howard Brown Health Center
🇺🇸Chicago, Illinois, United States
Community Research Initative
🇺🇸Boston, Massachusetts, United States
Brigham & Women's Hospital
🇺🇸Boston, Massachusetts, United States
Therapeutic Concepts, PA
🇺🇸Houston, Texas, United States
The Kinder Medical Group
🇺🇸Miami, Florida, United States
La Playa Medical Group and Clinical Research
🇺🇸San Diego, California, United States
Gordon E. Crofoot, MD, PA
🇺🇸Houston, Texas, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
Duke University
🇺🇸Durham, North Carolina, United States
Ospedale San Raffaele
🇮🇹Milano, Italy
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
🇺🇸Torrance, California, United States
Gary Richmond, MD, PA, Inc.
🇺🇸Fort Lauderdale, Florida, United States
Saint Michael's Medical Center
🇺🇸Newark, New Jersey, United States
The University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Spectrum Medical Group
🇺🇸Phoenix, Arizona, United States
Apex Research, LLC
🇺🇸Denver, Colorado, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Clinique OPUS
🇨🇦Montreal, Quebec, Canada
Sunnybrook Health Science Center
🇨🇦Toronto, Canada
Hospital del Mar
🇪🇸Barcelona, Spain
The University of South Florida
🇺🇸Tampa, Florida, United States
Infectious Disease Research Institute Inc.
🇺🇸Tampa, Florida, United States
St. Joseph's Comprenhensive Research Inisitute
🇺🇸Tampa, Florida, United States
DCOL Center for Clinical Research
🇺🇸Longview, Texas, United States
East Bay AIDS Center
🇺🇸Oakland, California, United States
Peter J. Ruane, MD, Inc.
🇺🇸Los Angeles, California, United States
Capital Medical Associates, P.C.
🇺🇸Washington, District of Columbia, United States
Infectious Diseases Associates
🇺🇸Pensacola, Florida, United States
Midway Immunology & Research Center, LLC
🇺🇸Fort Pierce, Florida, United States
Orlando Immunology Center
🇺🇸Orlando, Florida, United States
Atlanta ID Group, PC
🇺🇸Atlanta, Georgia, United States
University of Hawaii - Hawaii Center for AIDS
🇺🇸Honolulu, Hawaii, United States
Institute of Human Virology, University of Maryland
🇺🇸Baltimore, Maryland, United States
Be Well Medical Center
🇺🇸Berkley, Michigan, United States
Central West Clinical Research, Inc.
🇺🇸Saint Louis, Missouri, United States
Southwest C.A.R.E. Center
🇺🇸Santa Fe, New Mexico, United States
Jacobi Medical Center
🇺🇸Bronx, New York, United States
New York Hospital Queens
🇺🇸Flushing, New York, United States
North Shore University Hospital - Division of Infectious Diseases
🇺🇸Manhasset, New York, United States
Mount Sinai School of Medicine
🇺🇸New York, New York, United States
Rosedale Infectious Diseases
🇺🇸Huntersville, North Carolina, United States
Summa Health Care Center
🇺🇸Akron, Ohio, United States
University of South Carolina School of Medicine
🇺🇸Columbia, South Carolina, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
St. Hope Foundation, Inc.
🇺🇸Bellaire, Texas, United States
Garcias' Family Health Group
🇺🇸Harlingen, Texas, United States
Tarrant County Infectious Disease Associates
🇺🇸Fort Worth, Texas, United States
Clinical Alliance for Research & Education - Infectious Diseases, LLC (CARE-ID)
🇺🇸Annandale, Virginia, United States
Peter Shalit, MD
🇺🇸Seattle, Washington, United States
Holdsworth House Medical Practice
🇦🇺Darlinghurst, New South Wales, Australia
Taylor Square Private Clinic
🇦🇺Darlington, New South Wales, Australia
Albion Street Centre
🇦🇺Sydney, New South Wales, Australia
East Sydney Doctors
🇦🇺Sydney, New South Wales, Australia
Melbourne Sexual Health Clinic
🇦🇺Carlton, Victoria, Australia
Otto-Wagner-Spital, Sozialmedizinisches Zentrum Baumgartner Hoehe
🇦🇹Wien, Austria
CHU Saint-Pierre University Hospital
🇧🇪Brussels, Belgium
Hôpital Erasme-ULB
🇧🇪Anderlecht, Brussels, Belgium
The Ottawa Hospital
🇨🇦Ottawa, Ontario, Canada
Spectrum Health
🇨🇦Vancouver, British Columbia, Canada
Health Sciences Centre Winnipeg
🇨🇦Winnipeg, Manitoba, Canada
Clinique medicale l'Actuel
🇨🇦Montreal, Quebec, Canada
Maple Leaf Research
🇨🇦Toronto, Ontario, Canada
Clinique Medicale Du Quartier Latin
🇨🇦Montreal, Quebec, Canada
National Center for Global Health and Medicine AIDS Clinical Center
🇯🇵Shinjuku-ku, Tokyo, Japan
HOPE Clinical Research
🇵🇷San Juan, Puerto Rico
Hospital Germans Trias i Pujol
🇪🇸Badalona, Spain
Hospital Universitari Vall D'Hebron
🇪🇸Barcelona, Spain
Hospital Clinic i Provincial
🇪🇸Barcelona, Spain
Universitätsspital Bern
🇨🇭Berne, Switzerland
University Hospital Bellvitge
🇪🇸Barcelona, Spain
Centre Hospitalier Universitaire Vaudois
🇨🇭Lausanne, Switzerland
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
University Hospital, Zurich
🇨🇭Zurich, Switzerland
The HIV Netherland Australia Thailand, Thai Red Cross AIDS Research Center (The HIV-NAT)
🇹🇭Bangkok, Thailand
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Ramathibodi Hospital, Mahidol University
🇹🇭Bangkok, Thailand
Siriraj Hospital
🇹🇭Bangkok, Thailand
Chiang Mai University
🇹🇭Chiang Mai, Thailand
Chelsea & Westminster Hospital
🇬🇧London, United Kingdom
Khon Kaen University
🇹🇭Khon Kaen, Thailand
Bamrasnaradura Infectious Diseases Institute
🇹🇭Nonthaburi, Thailand
Yale University School of Medicine
🇺🇸New Haven, Connecticut, United States
Kaiser Permanente - Sacramento
🇺🇸Sacramento, California, United States
AIDS Research Consortium of Atlanta
🇺🇸Atlanta, Georgia, United States
Metrowest Medical Center
🇺🇸Framingham, Massachusetts, United States
AIDS Research and Treatment Center of the Treasure Coast
🇺🇸Vero Beach, Florida, United States
Whitman Walker Clinic
🇺🇸Washington, District of Columbia, United States
University of California, San Diego
🇺🇸San Diego, California, United States
Dupont Circle Physicians Group, P.C.
🇺🇸Washington, District of Columbia, United States
IDOCF/ValuHealthMD, LLC
🇺🇸Orlando, Florida, United States
Infectious Disease Specialist of Atlanta
🇺🇸Decatur, Georgia, United States
Baystate Infectious Diseases Clinical Research
🇺🇸Springfield, Massachusetts, United States
ID Care
🇺🇸Hillsborough, New Jersey, United States
The Miriam Hospital
🇺🇸Providence, Rhode Island, United States
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Southampton Healthcare, Inc.
🇺🇸Saint Louis, Missouri, United States
Central Texas Clinical Research
🇺🇸Austin, Texas, United States
Upstate Infectious Diseases Associates
🇺🇸Albany, New York, United States
Infectious Disease Consultants, PA
🇺🇸Charlotte, North Carolina, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Trinity Health and Wellness Center/AIDS Arms, Inc.
🇺🇸Dallas, Texas, United States
North Texas Infectious Diseases Consultants
🇺🇸Dallas, Texas, United States
Complejo Hospitalario Universitario de Santiago (CHUS)
🇪🇸Santiago de Compostela, Spain
DIAID, Department of Dermatology, Medical University Vienna
🇦🇹Vienna, Austria
University of California, Los Angeles
🇺🇸Los Angeles, California, United States
Albany Medical College
🇺🇸Albany, New York, United States
University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
AIDS Healthcare Foundation
🇺🇸Miami Beach, Florida, United States